Book A A, Wiley R G, Schweitzer J B
Department of Anatomy and Neurobiology, University of Tennessee, Memphis 38163.
J Neuropathol Exp Neurol. 1994 Jan;53(1):95-102. doi: 10.1097/00005072-199401000-00012.
An immunotoxin (IT) composed of a monoclonal antibody to the nerve growth factor (NGF) receptor, 192 IgG, chemically linked to saporin, 192 IgG-saporin, was shown to selectively reduce forebrain choline acetyltransferase (ChAT) activity in the rat brain following intraventricular administration. In order to determine if the IT was killing NGF receptor-positive neurons in the CBF (rather than simply suppressing the cholinergic phenotype in these cells), a population of neurons in the nucleus basalis magnocellularis (NBM) was prelabeled by an intracortical injection of the neurotracer Fluoro-Gold (FG) 1 week before intraventricular injections of IT or control substances (reduced IT or phosphate-buffered saline). We found that there were very few double-labeled (i.e. FG-labeled and ChAT-positive) neurons remaining in the NBM of IT-treated animals. The absolute number of FG-labeled neurons in the NBM of IT-treated animals was reduced by a number similar to the counts of double-labeled neurons in the NBM of control animals. Our conclusion is that the IT is preferentially lethal to cholinergic neurons in the NBM. Due to its ability to selectively kill cholinergic neurons in the CBF and concomitantly spare noncholinergic neurons with similar morphology and projections, 192 IgG-saporin can be used to produce a selective model of CBF deficit in the rat.
一种免疫毒素（IT），由针对神经生长因子（NGF）受体的单克隆抗体192 IgG与皂草素化学连接而成，即192 IgG-皂草素，经脑室注射后可选择性降低大鼠前脑胆碱乙酰转移酶（ChAT）的活性。为了确定该免疫毒素是否正在杀死基底前脑（CBF）中NGF受体阳性神经元（而不是简单地抑制这些细胞中的胆碱能表型），在脑室注射免疫毒素或对照物质（减量免疫毒素或磷酸盐缓冲盐水）前1周，通过向皮质内注射神经示踪剂荧光金（FG）对基底大细胞核（NBM）中的一群神经元进行预标记。我们发现，接受免疫毒素治疗的动物的NBM中几乎没有双标记（即FG标记且ChAT阳性）的神经元残留。接受免疫毒素治疗的动物的NBM中FG标记神经元的绝对数量减少的数量与对照动物的NBM中双标记神经元的数量相似。我们的结论是，该免疫毒素对NBM中的胆碱能神经元具有优先致死性。由于其能够选择性杀死CBF中的胆碱能神经元，并同时使具有相似形态和投射的非胆碱能神经元免受影响，1,92 IgG-皂草素可用于建立大鼠CBF缺陷的选择性模型。
